The objectives of this study are: to compare efficacy and safety of the combination of PEG-IFN and Ribavarin given for 48 weeks with REBETRON given for 48 weeks in the treatment of patients with chronic hepatitis C virus (HCV); to compare the efficacy and safety of the combination therapy to PEG-IFN monotherapy when each is given for 48 weeks; to compare the efficacy of three treatment regimens according to HCV genotype; and to determine if there is any pharmacokinetic interaction between PEG-IFN and ribavarin. Interferon is the only approved monotherapy for chronic hepatitis C (CHC), but it results in a sustained response rate of only about 15-20% in the general CHC populations. Ribavirin is a guanosine analogue that inhibits the viral replication of many RNA and DNA viruses, such as CHC and may also normalize serum ALT activity and/or improve liver histology; still, relapse occurs in a majority of patients treated with ribavirin alone. Hoffman-La Roche has recently developed a chemically modified interferon called Pegylated-Interferon Alfa-2a (PEG-IFN). PEG-IFN is able to circulate in the blood much longer than its parent compound, and pharmacokinetic and pharmacodynamic data from animal tests have suggested that PEG-IFN could possibly be up to three times as effective as interferon alone. Furthermore, sustained and improved response rates have resulted from the combination of ribavirin and interferon in the treatment of CHC, proving to be more than twice as successful as IFN montherapy, without any substantial risks. Based on these factors, Hoffman-LaRoche (the study sponsor) has designed this study to test whether ribavirin will enhance the efficacy of PEG-IFN in the same manner as for IFN. The enhanced virologic response rates seen with PEG-IFN compared to IFN and the improved efficacy of combination therapy over IFN monotherapy suggests that combining PEG-IFN and ribavirin may result in valuable therapy for the future treatment of chronic hepatitis C. Subjects will be adult members of the population who have been diagnosed with chronic hepatitis C, and who have never been treated with interferon or ribavirin at any time. There will be a total of 825 subjects participating in this study at up to 100 institutions worldwide, and Columbia-Presbyterian Medical Center is expected to enroll up to 10 patients. The first part of the study is a 35 day screening process to determine eligibility. The second part of the study is a 48-week treatment process. Patients will be randomized to one of the following three groups: Group 1 REBETRON; Group 2 PEG-IFN + ribavirin; Group 3 PEG-IFN + placebo. Patients will return to the clinic for regular check-ups on weeks 1,2,4,6, and 8, and every 4 weeks for the rest of the 48-week treatment period. These visits during the treatment period will consist of a physical examination, blood drawing (up to 2 tablespoons) and the occasional urine sample collection. The third part of the study is a 24-week observation period, where patients will be evaluated every 4 weeks for the effects of the test drugs. At weeks 52, 60, and 72 study patients are expected to have laboratory tests; at week 68, only blood samples will need to be drawn